Cancer Res Treat.  2021 Oct;53(4):1072-1083. 10.4143/crt.2020.1024.

Combination of Simvastatin and FAC Improves Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

• Yulian ED
• Siregar NC
• B

• KMID: 2521582
• DOI: http://doi.org/10.4143/crt.2020.1024

Abstract

Purpose
The efficacy of neoadjuvant chemotherapy for locally advanced breast cancer (LABC) is limited due to drug resistance and cardiotoxic effects. Preclinical studies have shown that statin induces apoptosis and decreases breast cancer cell growth. This study aims to evaluate the role of statin in combination with fluorouracil, adriamycin, and cyclophosphamide (FAC) therapy in LABC patients.
Materials and Methods
We undertook a randomized, double-blinded, placebo-controlled trial in two centers of Indonesia. Patients were randomly assigned to FAC plus simvastatin (40 mg/day orally) or FAC plus placebo (40 mg/day) for 21 days. The FAC regimen was repeated every 3 weeks. We evaluated the clinical response, pathological response, and toxicities.
Results
The objective response rate (ORR) for FAC plus simvastatin was 90% (95% confidence interval [CI], 0.99 to 1.67) by per-protocol analysis. No complete responses (CR) were recorded, but there were 48 partial responses. No significant difference was observed between the two groups with the ORR (p=0.103). The pathological CR rate was 6.25% (2 in simvastatin group and 1 in placebo group). Adverse events in both arms were generally mild, mainly consisted of myotoxicity. Human epidermal growth factor receptor 2 (HER2) expression was a factor related to the success of therapeutic response (odds ratio, 4.2; 95% CI, 1.121 to 15.731; p=0.033).
Conclusion
This study suggests that simvastatin combined with FAC shows improvements in ORR and pathological response in patients with LABC. Although no statistically significant difference was documented, there was a trend for better activity and tolerability. The addition of 40 mg simvastatin may improve the efficacy of FAC in LABC patients with HER2 overexpression.

Keyword

Neoadjuvant therapy; Breast neoplasms; FAC; Simvastatin

Figure

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  Fig. 1 Consort flow chart of this study. From 70 eligible patients, 60 patients completed the trial and were evaluated in this study.

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  Fig. 2 Histological image representative of grade 5 Miller-Payne system as a pathological complete response. H&E staining was used in the histopathological evaluation: (A) atypic cells (×100) and (B) foam and giant cells (×100).

Reference

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